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Simple Summary Throughout the life history of giant pandas, we have found that captive and wild giant pandas have significantly different parenting experiences. To summarize the breeding history of the Chengdu Research Base of Giant Panda Breeding over the past 30 years, we found that the parenting experience is related to the natural mating ability of captive male giant pandas. However, there are few studies on the effects of different nursing methods on the behavioral expression of captive giant pandas, mainly focusing on the behavioral development of captive giant panda cubs, but the effects on the behavioral adaptive expression and stress of adult females have not been reported. From the perspective of adult female giant pandas in the nursery period, this experiment attempts to clarify whether different nursing methods in the cub-rearing period will affect the behavioral adaptive expression of the dams. We aim to understand whether confinement mode may cause stress problems in adult captive giant pandas, and provide a scientific basis for improving the design parameters of nursery pens and improving the welfare level of captive giant pandas. Based on the current results, we find that, in the current captive environment, singleton and parent rearing are kinds of nursing methods that are in accordance with the characteristics of the natural nursing of giant pandas and have little effect on the mother–cub relationship and welfare of captive adult female giant pandas. Abstracts Nursing protocols in giant panda conservation breeding programs often strongly deviate from the natural cub-rearing behaviors observed in situ, potentially affecting the expression of species-typical behavior in both dams and cubs. To evaluate the effects of different nursing methods on the behavioral expression of captive adult female giant pandas, it is necessary to understand such effects due to unnatural human interference to improve the welfare of giant pandas in captive breeding conditions. In this study, we selected nine captive adult female giant pandas managed with different nursing methods as the research objects. Behavioral observations were performed during the early nursing period (1–90 d). Compared with the artificially assisted nursing method, captive adult female giant pandas who adopted the singleton and parent nursing method exhibited a significantly longer time engaged in mother–cub interaction behavior and invested a significantly smaller portion of their daily time budget on pacing and railing-directed behavior in the three months postpartum. However, no significant differences in the percentage of time exhibiting maternal behaviors were noted between the different nursing methods. In conclusion, in the current captive environment, singleton and parent rearing was a kind of nursing method that matched natural cub-rearing characteristics and was less stressful for captive adult giant pandas.

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) constitute a class of cells with significant self-renewal and multilineage differentiation properties and have great potential for therapeutic applications and the genetic conservation of endangered animals. In this study, we successfully isolated and cultured UC-MSCs from the blood vessels of giant panda umbilical cord (UC). The cells were arranged in a vortex or cluster pattern and exhibited a normal karyotype, showing the morphological characteristics of fibroblasts. In addition, we found that basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) promoted cell proliferation, whereas stem cell factor (SCF) did not promote cell proliferation. Cultured UC-MSCs were negative for CD34 (hematopoietic stem cell marker) and CD31 (endothelial cell marker), but positive for MSC markers (CD44, CD49f, CD105, and CD73) and stem cell markers (KLF4, SOX2, and THY1). Similar to other MSCs, giant panda UC-MSCs have multiple differentiation ability and can differentiate into adipocytes, osteoblasts and chondrocytes. Giant panda UC-MSCs are new resources for basic research as cell models following their differentiation into different cell types and for future clinical treatments of giant panda diseases.

Background Parasitic infections are among the important causes of death of giant pandas (Ailuropoda melanoleuca) that hamper their survival in the wild. There are about 35 species of parasites which have been identified in giant pandas, but no information is currently available regarding the infection of Babesia in giant pandas. Babesia spp. are common intraerythrocytic parasite in wildlife, transmitted by ixodid ticks, which cause babesiosis. Clinical signs of babesiosis include fever, hemolysis, anemia, jaundice and death. Methods A species of Babesia was detected in the blood of a giant panda based on morphology and PCR amplification of the 18S rRNA gene. The phylogenetic relationship of Babesia sp. infecting giant panda was assessed by gene sequence alignment and phylogenetic analysis. Results Our analysis revealed that the Babesia isolate detected was most similar to an unidentified species of Babesia identified in black bears (Ursus thibetanus japonicus) from Japan (Babesia sp. Iwate, AB586027.1) with a 99.56% sequence similarity, followed by Babesia sp. EBB (AB566229.1, 99.50%) and Babesia sp. Akita (AB566229.1, 99.07%). Conclusions To our knowledge, this is the first report of Babesia detected in the giant panda. The results indicate that this Babesia sp. may be a novel species, currently named Babesia sp. strain EBP01.

Polycyclic aromatic hydrocarbon (PAH) emissions from the combustion of household solid coal for cooking and heating cause great harm to public health in China, especially in less developed areas. Children are one of the most susceptible population groups at risk of indoor air pollutants due to their immature respiratory and immune systems. However, information on PAH exposure of children is limited due to limited monitoring data. In this study, we aimed to assess the seasonal differences of PAHs in classrooms, analyze the pollutant sources, and calculate the incremental lifetime cancer risk attributable to PAHs in Shanxi Provence. A typical school using household coal combustion in Shanxi Province was selected. Fine particulate matter (PM2.5)samples were collected by both individual samplers and fixed middle-flow samplers during the heating and non-heating seasons in December 2018 and April 2019. The PAH concentrations in PM2.5 samples were analyzed by a gas chromatograph coupled to a mass spectrometer. The results showed that PAH concentrations in PM2.5 varied between 89.1 ng/m3 in the heating season and 1.75 ng/m3 in the non-heating season. The mean concentrations of benzo[a]pyrene (BaP), a carcinogenic marker of PAHs, were 10.3 and 0.05 ng/m3 in the heating and non-heating seasons, respectively. Source allocation analysis of individual portable and passive samplers revealed that the main contributors during heating and non-heating seasons were coal combustion and gasoline sources, respectively. According to the results of a Monte Carlo simulation, the incremental lifetime cancer risk values from the inhalation of PAHs in the heating and non-heating seasons were 3.1 &times, 10&minus, 6 and 5.7 &times, 8, respectively. The significant increase in PAHs and the incremental lifetime cancer risk in the heating season indicates that children are more exposed to health threats in winter. Further PAH exposure control strategies, including reducing coal usage and promoting clean fuel applications, need to be developed to reduce the risk of PAH-induced cancer.

TH17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for TH17 cell regulation, however, remain elusive, especially regulation at the post-transcriptional level. Tristetraprolin (TTP) is an RNA-binding protein important for degradation of the mRNAs encoding several proinflammatory cytokines. With newly generated T cell-specific TTP conditional knockout mice (CD4CreTTPf/f), we found that aging CD4CreTTPf/f mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector TH17 cells in the affected skin. TTP inhibited TH17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4CreTTPf/f mice displayed severe colitis and had more TH17 cells and serum IL-17A compared with wild-type mice. Furthermore, neutralization of IL-17A reduced the severity of colitis. Our results reveal a new mechanism for regulating TH17 function and TH17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of TH17-mediated diseases.

BACKGROUND/OBJECTIVE The giant panda belongs to the family Ursidae and, as a species of bear, still retains the simple digestive system of a Carnivoran. However, under the pressure of a specific habitat they had to adapt to a plant mono-diet consisting of bamboo with different species and growth stages around the year. A plant-based diet has relatively low iodine content with risk of iodine deficiency. Furthermore, bamboo contains cyanogenic glycosides releasing cyanide whose detoxification metabolite the thiocyanate acts as antagonist against iodine uptake and storage in the thyroid. To date very little is known about the iodine nutritional status of the giant panda, thus this study was conducted to receive the first information about the iodine nutrition of captive giant panda. SUBJECTS/METHODS Here we investigated the iodine content of bamboo with different plant parts/vegetation stage and species and further compounds of the captive giant panda diet. Next, the urinary iodine (UI) and urinary thiocyanate (UT) levels of infant, sub-adult, adult and geriatric captive giant pandas was measured during the periods when the pandas consume both bamboo leaves- and culm (bamboo leaf-culm stage). Afterwards, the UI of 19 adult giant pandas was measured again for the different iodine intake during bamboo shoot stage. Finally, in this study part also the fecal iodine concentration was analyzed for calculation of total iodine excretion in relation to the iodine intake. RESULTS Bamboo leaves had the highest iodine content (453 μg/kg dry matter (DM)), followed by the shoots (84 μg/kg DM, p

Giant pandas (Ailuropoda melanoleuca) were historically hunted using dogs and are currently threatened by free-roaming dogs and their associated diseases. To better understand the spatial magnitude of this threat, we used a GIS approach to investigate edge effects of dogs on giant panda habitat. We first examined two nature reserves with contrasting free-roaming dog populations: Liziping, with many dogs (~0.44/km2), and Daxiangling, with few dogs (~0.14/km2). Spatial analysis indicated that giant pandas at Liziping (but not Daxiangling) showed a shift in habitat use away from populated areas consistent with a risk response to the foray distance of free-roaming dogs (10.9 km path-distance). Most giant panda locations (86%) from the 2014 census in Liziping were clustered around remote “dog-free zones.” Expanding this analysis across the entire giant panda range revealed that 40% of panda habitat is within the foray distance of dogs. Our assessment will inform dog control programs including monitoring, education, veterinary care, and other measures. We recommend that reserves designated for the release of translocated pandas receive priority consideration for dog control efforts. Only by understanding and managing complex interactions between humans, domestic animals, and wild animals can we sustain natural systems in a world increasingly dominated by humans.

Background The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains in southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations between metabolite types and bacterial genus were detected. Conclusions There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.

Depicting a taxonomic group's evolutionary trajectory as a function of changes in the geographical landscape and its historical distribution is critical for constructing informed conservation strategies. Based on fossil sites from the Pliocene to the Holocene, and historical records since 1175 AD, we established macaques’ dispersal pathways into and through China. These routes include internal pathways starting from the southeast corner of the Qinghai‐Tibet Plateau and Mts. Hengduan in western China, and the routes through the estuaries of the three major rivers (Yangtze, Yellow, and Pearl). Our results indicate that macaques used the three rivers and avoided the higher elevation of the plateaus to promote their radiation. They occupied the whole mainland and islands in the Pleistocene and experienced shrunken distribution in the Holocene due to climate changes and human‐induced activities. A prominent China‐wide reduction occurred between 1817 and 1917; and a remarkable retraction from central China happened between 1918 and 2018 following further eco‐social development and human expansion in central China, particularly since the second half of the last century. Starting in 1175 there was a restriction of range to higher altitudes, so that macaques have contracted their range to the west, and the Qinghai‐Tibet Plateau and Mts. Hengduan have become an important sanctuary. We predict that if the current climate and human‐induced changes are not reversed by decisive conservation actions, macaques in east and central China will likely be extinct in the near future., Dispersal and radiation pathways undergone by the macaques (Macaca) during the processes of colonising East Asia in the Pliocene, Pleistocene and Early Holocene., Research highlights Major waterways used by the primates to disperse and radiate in ChinaPrimate evolution and dispersion in East Asia from the Pliocene to the Early HoloceneHistorically shrunk macaque distribution in China

Giant pandas represent one of the most endangered species worldwide, and their reproductive capacity is extremely low. They have a relatively long gestational period, mainly because embryo implantation is delayed. Giant panda cubs comprise only a small proportion of the mother's body weight, making it difficult to determine whether a giant panda is pregnant. Timely determination of pregnancy contributes to the efficient breeding and management of giant pandas. Meanwhile, metabolomics studies the metabolic composition of biological samples, which can reflect metabolic functions in cells, tissues, and organisms. This work explored the urinary metabolites of giant pandas during pregnancy. A sample of 8 female pandas was selected. Differences in metabolite levels in giant panda urine samples were analyzed via ultra-high-performance liquid chromatography/mass spectrometry comparing pregnancy to anoestrus. Pattern recognition techniques, including partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis, were used to analyze multiple parameters of the data. Compared with the results during anoestrus, multivariate statistical analysis of results obtained from the same pandas being pregnant identified 16 differential metabolites in the positive-ion mode and 43 differential metabolites in the negative-ion mode. The levels of tryptophan, choline, kynurenic acid, uric acid, indole-3-acetaldehyde, taurine, and betaine were higher in samples during pregnancy, whereas those of xanthurenic acid and S-adenosylhomocysteine were lower. Amino acid metabolism, lipid metabolism, and organic acid production differed significantly between anoestrus and pregnancy. Our results provide new insights into metabolic changes in the urine of giant pandas during pregnancy, and the differential levels of metabolites in urine provide a basis for determining pregnancy in giant pandas. Understanding these metabolic changes could be helpful for managing pregnant pandas to provide proper nutrients to their fetuses.

TH17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for TH17 cell regulation, however, remain elusive, especially regulation at the post-transcriptional level. Tristetraprolin (TTP) is an RNA-binding protein important for degradation of the mRNAs encoding several proinflammatory cytokines. With newly generated T cell-specific TTP conditional knockout mice (CD4CreTTPf/f), we found that aging CD4CreTTPf/f mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector TH17 cells in the affected skin. TTP inhibited TH17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4CreTTPf/f mice displayed severe colitis and had more TH17 cells and serum IL-17A compared with wild-type mice. Furthermore, neutralization of IL-17A reduced the severity of colitis. Our results reveal a new mechanism for regulating TH17 function and TH17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of TH17-mediated diseases.

Sperm cryopreservation is an essential approach for assisted reproduction and genetic resources conservation in captive giant pandas. Cryopreservation, however, leads to a significant decrease in sperm quality and, consequently, a low fertilization rate. Therefore, it is mandatory to disclose more suitable and efficient freezing strategies for sperm cryopreservation. In the present study, we compared for the first time the performance of two commercial freeze extender (INRA96 versus TEST) freezing methods on post-thawed semen quality. Semen cryopreserved with the INRA96 showed better total motility (73.00 ± 4.84% vs 57.56 ± 3.60%, P 0.001), membrane integrity (60.92 ± 2.27% vs 40.53 ± 2.97%, P 0.001) and acrosome integrity (90.39 ± 2.74% vs 84.26 ± 4.27%, P 0.05) than stored with TEST. There was no significant difference in DNA integrity after thawing between the two extenders (95.69 ± 3.60% vs 94.26 ± 4.84%). In conclusion, the INRA96 method showed to be better for giant panda sperm cryopreservation and should therefore be recommended for use in order to increase success of artificial insemination.

Role of long non-coding RNA (lncRNA) PICART1 in alleviating the progression of cervical cancer (CC) via targeting TCF21 was elucidated. PICART1 level in CC and paracancerous tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Its level in CC patients with different tumor stages (stage I+II and stage III+IV) and tumor sizes (≤4 cm and >4 cm) was examined. Survival analysis was conducted in CC patients expressing high level and low level of PICART1. Changes in proliferative, migratory and invasive abilities of HeLa and SiHa cells after transfection of si-PICART1 were assessed. Prognostic value of TCF21 in CC was determined by Kaplan-Meier curves. The interaction between PICART1, TCF21 and ARID1A was investigated through RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assay. PICART1 was downregulated in CC tissues and cell lines. CC patients with worse TNM staging and larger tumor size presented lower level of PICART1. Low level of PICART1 in CC patients predicted a worse prognosis. Silence of PICART1 stimulated the proliferative, migratory and invasive abilities of HeLa and SiHa cells. TCF21 expression was low in CC tissues and positively regulated by PICART1. Low level of TCF21 in CC patients predicted a worse prognosis. Potential binding relationship was verified among PICART, ARID1A and TCF21. ChIP assay confirmed the decreased enrichment of ARID1A in TCF21 promoter region after PICART1 knockdown. lncRNA PICART1 recruits ARID1A to activate TCF21 expression, thus alleviating the malignant progression of CC.

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.

The present study investigated the survival benefit of non–anthracycline (ANT)-based vs ANT-based regimens in a large-scale, real-world cohort of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL). Within the China Lymphoma Collaborative Group (CLCG) database (2000-2015), we identified 2560 newly diagnosed patients who received chemotherapy with or without radiotherapy. Propensity score matching (PSM) and multivariable analyses were used to compare overall survival (OS) and progression-free survival (PFS) between the 2 chemotherapy regimens. We explored the survival benefit of non–ANT-based regimens in patients with different treatments in early-stage disease and in risk-stratified subgroups. Non–ANT-based regimens significantly improved survivals compared with ANT-based regimens. The 5-year OS and PFS were 68.9% and 59.5% for non–ANT-based regimens compared with 57.5% and 44.5% for ANT-based regimens in the entire cohort. The clinical advantage of non–ANT-based regimens was substantial across the subgroups examined, regardless of stage and risk-stratified subgroup, and remained significant in early-stage patients who received radiotherapy. The survival benefits of non–ANT-based regimens were consistent after adjustment using multivariable and PSM analyses. These findings provide additional evidence supporting non–ANT-based regimens as a first-line treatment of patients with ENKTCL.

Background: Several epidemiological studies have been performed to evaluate the association of dietary intake of vitamin C-oriented foods (DIVCF) with risk of fracture and bone mineral density (BMD) loss, but the results remain controversial. Therefore, we conducted a systematic meta-analysis to assess this correlation. Methods: We searched EmBase, PubMed, Web of Science, and the Chinese database CNKI for relevant articles published up to August 2019. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random- or fixed-effects model. Discrepancies were resolved by consultation with a third expert. Results: A total of 13 eligible articles (including 17 studies) with 19,484 subjects were identified for the present meta-analysis. The pooled RR of hip fracture for the highest vs. lowest category was 0.66 (95% CI, 0.47–0.94) for DIVCF, i.e., people with a greater frequency of Vitamin C uptake had a 34% (95% CI, 6%−53%) lower prevalence of hip fracture. In subgroup analyses stratified by study design, gender, and age, the negative associations were statistically significant. Furthermore, the statistical analysis of the association between DIVCF and risk of osteoporosis (RR, 0.66; 95% CI, 0.48–0.92), BMD at the lumbar spine (pooled r, 0.15; 95% CI, 0.09–0.23), and BMD at the femoral neck (pooled r, 0.20; 95% CI, 0.11–0.34) showed beneficial effects of DIVCF. Conclusion: Our meta-analysis indicates that DIVCF is negatively associated with the risk of hip fracture, osteoporosis, and BMD loss, suggesting that DIVCF decreases the risk of hip fracture, osteoporosis, and BMD loss.

Golden snub-nosed monkeys are endangered animals in China, and their cells have been demonstrated to be important as genetic resources and in applications for advancing biological research. Moreover, in primary research, basic fibroblast growth factor (bFGF) is used to promote the proliferation of fibroblasts to create abundant cells for cryopreservation. To further investigate the effect of bFGF on the efficiency of preservation of fibroblasts obtained from an endangered species, a fibroblast cell line was isolated from a dead golden snub-nosed monkey. Cell viability and mitochondrial membrane potential were assessed using CCK8 and JC-1 assay kits. The karyotype was analyzed by chromosomal microarray analysis, while RNA sequencing and gene expression analyses were performed to assess molecular changes in response to bFGF. Flow cytometry was used to characterize changes in cell surface markers in response to bFGF treatment. The results showed that cells maintained typical fibroblast morphology, while cell viability and mitochondrial membrane potential were not significantly affected between three and eight passages (p 0.05). We also observed that the addition of bFGF promoted fibroblast proliferation and increased mitochondrial membrane potential. In addition, the bFGF treatment did not alter the normal karyotype of cells, downregulating fibroblast-associated genes and upregulating those associated with cell regulation, including those of the WNT, PI3K and MAPK pathways. The addition of bFGF also increased CD29, CD90, CD105, CD34 and CD44 expression while decreasing that of CD14 and HLA-DR at the protein level. Taken together, these results demonstrate that bFGF may upregulate the WNT, PI3K and MAPK pathways to promote cell proliferation while also increasing the expression of genes and surface markers associated with mesenchymal and hematopoietic cell linages.

Background Disease prevention and control is a significant part during the ex-situ conservation of the red panda (Ailurus fulgens) with bacterial infection being one of the important threats to the health of the captive population. So far, there was no systematic and detailed publications about the red panda-related E. coli disease. This study was conducted for the purpose of determining the cause of death, etiology and pathogenesis on a red panda through clinical symptoms, complete blood count, biochemical analysis, pathological diagnosis, antimicrobial susceptibility test, mouse pathogenicity test, and bacterial whole genome sequencing.Results A bacterial strain confirmed as Uropathogenic Escherichia coli (UPEC) was isolated from one captive dead red panda, which is resistant to most of the β-lactam drugs and a small number of aminoglycoside medications. The mouse pathogenicity test results showed the strains isolated postmortem from mice were the same as from the dead red panda, and the pathological findings were similar to the red panda while they were not completely the same. These pathological differences between red panda and mice may be related to the routes of infection and perhaps species differences and tolerance. The whole genome sequencing results showed that the isolated strain contained P pili, type I pili and iron uptake system related factors, which were closely related to its nephrotoxicity. Conclusion The red panda died of bacterial infection which was identified as Uropathogenic Escherichia coli. The pathogenic mechanisms of the strain are closely related to the expression of specific virulence genes.

Characteristics of the gut microbiome vary synchronously with changes in host diet. However, the underlying effects of these fluctuations remain unclear. Here, we performed fecal microbiota transplantation (FMT) of diet-specific feces from an endangered mammal (the giant panda) into a germ-free mouse model. We demonstrated that the butyrate-producing bacterium Clostridium butyricum was more abundant during shoot-eating season than during the leaf-eating season, congruent with the significant increase in host body mass. Following season-specific FMT, the microbiota of the mouse model resembled that of the donor, and mice transplanted with the microbiota from the shoot-eating season grew faster and stored more fat. Mechanistic investigations revealed that butyrate extended the upregulation of hepatic circadian gene Per2, subsequently increasing phospholipid biosynthesis. Validation experiments further confirmed this causal relationship. This study demonstrated that seasonal shifts in the gut microbiome affect growth performance, facilitating a deeper understanding of host-microbe interactions in wild mammals.

An organism’s fitness is tied closely to its ability to obtain food. However, many foods are nutritionally suboptimal on their own, forcing an individual to develop a feeding strategy that actively manages both type and amount of food consumed. Animals in captivity are additionally limited to human provisioned diets, which may be nutritionally inadequate and negatively affect behavior and health. We studied the nutritional intake of captive golden snub-nosed monkeys (Rhinopithecus roxellana) at two locations in China (132 days of continuous, sunrise to sunset focal samples of 7 individuals at each site) and used the Geometric Framework for nutrition to identify their feeding strategy and evaluate diet variation across sites, seasons, and age–sex classes. Captive golden snub-nosed monkeys had a mean nutrient intake of 75% carbohydrates (15% neutral detergent fiber, 60% total nonstructural carbohydrates), 12% fat, and 13% protein (by energy) that differed by location and season owing to differences in the type and amount of food items offered and consumed. Intake at one location differed from that of wild golden snub-nosed monkeys, suggesting that the captive diet was inadequate. These results highlight the importance of developing nutritionally adequate diets for captive animals based on an understanding of their nutritional requirements.

Embryonic diapause occurs in over 130 species of mammals. In embryonic diapause, there is a reversible cessation phase in embryo development and subsequent reactivation and continuation of development with no adverse effects. This allows animals to prolong gestation and give birth to offspring at a more favorable time from a survival perspective. Embryonic diapause is divided into two types: facultative diapause which is induced by physiological conditions and obligate diapause which is induced by season of the year. The process of embryonic diapause includes three phases: onset, maintenance, and reactivation. With facultative diapause the suckling stimulus promotes secretion of prolactin, which suppresses development and secretion activity of the corpus luteum (CL). The decrease of progesterone, secreted by CL, subsequently results in embryos in the diapause state. The embryonic diapause that occurs in mink is of the obligate type and is regulated by photoperiod. The short daylight (12 h) before the vernal equinox induces an increase in the release of melatonin from the pineal gland. The secretion of prolactin is suppressed and the production of progesterone from CL is reduced. During these phases, many others factors that regulate embryonic and uterine status, hormonal profile, polyamines, and uterine secretion, have been monitored. In recent times, the understanding of the role of different molecular events in embryonic diapause has been advanced. The present review summarizes the research advances related to embryonic diapause to enhance the understanding of this phenomenon and to be considered when there are future research endeavors related to embryonic diapause.

This study evaluated the survival benefit of intensity-modulated radiation therapy (IMRT) compared with 3-dimension conformal radiation therapy (3D-CRT) in a large national cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). This retrospective study reviewed patients with early-stage NKTCL treated with high-dose radiation therapy (RT; ≥45 Gy) at 16 Chinese institutions. Patients were stratified into 1 of 4 risk groups based on the number of risk factors: low risk (no factors), intermediate-low risk (1 factor), intermediate-high risk (2 factors), and high-risk (3-5 factors). Of the 1691 patients, 981 (58%) received IMRT, and 710 (42%) received 3D-CRT. Unadjusted 5-year overall survival (OS) and progression-free survival (PFS) were 75.9% and 67.6%, respectively, for IMRT compared with 68.9% (P = .004) and 58.2% (P < .001), respectively, for 3D-CRT. After propensity score match and multivariable analyses to account for confounding factors, IMRT remained significantly associated with improved OS and PFS. The OS and PFS benefits of IMRT persisted in patients treated with modern chemotherapy regimens. Compared with 3D-CRT, IMRT significantly improved OS and PFS for high-risk and intermediate-high–risk patients but provided limited benefits for low-risk or intermediate-low–risk patients. A risk-adapted survival benefit profile of IMRT can be used to select patients and make treatment decisions.

Research is a highly competitive profession where evaluation plays a central role; journals are ranked and individuals are evaluated based on their publication number, the number of times they are cited and their h-index. Yet such evaluations are often done in inappropriate ways that are damaging to individual careers, particularly for young scholars, and to the profession. Furthermore, as with all indices, people can play games to better their scores. This has resulted in the incentive structure of science increasingly mimicking economic principles, but rather than a monetary gain, the incentive is a higher score. To ensure a diversity of cultural perspectives and individual experiences, we gathered a team of academics in the fields of ecology and evolution from around the world and at different career stages. We first examine how authorship, h-index of individuals and journal impact factors are being used and abused. Second, we speculate on the consequences of the continued use of these metrics with the hope of sparking discussions that will help our fields move in a positive direction. We would like to see changes in the incentive systems, rewarding quality research and guaranteeing transparency. Senior faculty should establish the ethical standards, mentoring practices and institutional evaluation criteria to create the needed changes.

To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway (UPP), and discuss the action of acupuncture in intervening heroin-induced brain damage. Thirty male Sprague-Dawley (SD) rats were divided into a control group, a model group and an acupuncture group by using the random number table. Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose. Afterwards, the injection was suspended for 5 d for withdrawal. The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times. The control group followed the step of the model establishment, but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal; the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage; the acupuncture group was dealt in the same way as the model group at the addiction stage, but received acupuncture at Baihui (GV 20) and Dazhui (GV 14) at the withdrawal stage, with the needles retained for 30 min each time, 1 session a day, for successive 5 d. On the 39th day, brain tissues were extracted from the hippocampus and ventral tegmental area (VTA) of the three groups of rats. The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL). The mRNA and protein expressions of ubiquitin (Ub), ubiquitin protein ligase (E3) and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR). Compared with the model group, rat’s hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining (P

Background/Aims: Giant pandas, an endangered species, are a powerful symbol of species conservation. Giant pandas may suffer from a variety of diseases. Owing to their highly specialized diet of bamboo, giant pandas are thought to have a relatively weak ability to resist diseases. The spleen is the largest organ in the lymphatic system. However, there is little known about giant panda spleen at a molecular level. Thus, clarifying the regulatory mechanisms of spleen could help us further understand the immune system of the giant panda as well as its conservation. Methods: The two giant panda spleens were from two male individuals, one newborn and one an adult, in a non-pathological condition. The whole transcriptomes of mRNA, lncRNA, miRNA, and circRNA in the two spleens were sequenced using the Illumina HiSeq platform. EBseq and IDEG6 were used to observe the differentially expressed genes (DEGs) between these two spleens. Gene Ontology and KEGG analyses were used to annotate the function of DEGs. Furthermore, networks between non-coding RNAs and protein-coding genes were constructed to investigate the relationship between non-coding RNAs and immune-associated genes. Results: By comparative analysis of the whole transcriptomes of these two spleens, we found that one of the major roles of lncRNAs could be involved in the regulation of immune responses of giant panda spleens. In addition, our results also revealed that microRNAs and circRNAs may have evolved to regulate a large set of biological processes of giant panda spleens, and circRNAs may function as miRNA sponges. Conclusion: To our knowledge, this is the first report of lncRNAs and circRNAs in giant panda, which could be a useful resource for further giant panda research. Our study reveals the potential functional roles of miRNAs, lncRNAs, and circRNAs in giant panda spleen.

A wild adult male giant panda that was rescued from a nature reserve in Sichuan Province, China, has died. The panda had been in poor physical condition: it was wheezing and had increased serum amylase. A pathological examination was performed in order to determine the cause of death. Gross examination revealed 1380 mL of yellowish fluid in the abdominal cavity, 356 nematodes in the digestive tract and one filling the pancreatic duct, contractions and variably-sized dark purple areas in the spleen, a collapsed right lung and consolidation of the left lung. Acute pancreatitis was confirmed histopathologically via edema, focal necrosis and hemorrhage with inflammatory cell infiltration. Other major histopathological changes included serous-hemorrhagic pneumonia, lymphocytic necrosis and depletion in the spleen, and degeneration and necrosis of renal tubular epithelial cells. The nematodes were identified as Baylisascaris schroederi via molecular assays. In conclusion, the cause of death of the giant panda was determined to be multiple organ dysfunction syndrome caused by baylisascariasis-induced acute pancreatitis. To our knowledge, this is the first report of fatal baylisascariasis-induced acute pancreatitis in the giant panda.

As we know, the periodic functions are symmetric within a cycle time, and it is meaningful to generalize the periodicity into more general cases, such as almost periodicity or almost automorphy. In this work, we introduce the concept of Poisson Sγ2-pseudo almost automorphy (or Poisson generalized Stepanov-like pseudo almost automorphy) for stochastic processes, which are almost-symmetric within a suitable period, and establish some useful properties of such stochastic processes, including the composition theorems. In addition, we apply a Krasnoselskii–Schaefer type fixed point theorem to obtain the existence of pseudo almost automorphic solutions in distribution for some semilinear stochastic differential equations driven by Lévy noise under Sγ2-pseudo almost automorphic coefficients. In addition, then we establish optimal control results on the bounded interval. Finally, an example is provided to illustrate the theoretical results obtained in this paper.

Through the implementation of giant panda ex situ conservation breeding programs, the giant panda has successfully been protected and has attained many conservation achievements. As of 2019, there were nearly 600 captive giant pandas worldwide, and the number of captive populations and the richness of genetic diversity have basically reached a self-sustainable state. However, to date, most captive adult male giant pandas do not mate naturally, and the reason is unclear, which has serious implications for implementation of the reintroduction training program of captive giant pandas. We used a combination of methods evaluating life history traits, behavioral observation, and bioinformatics statistical analysis and conducted comprehensive research on the factors that affected the natural mating success rates of captive adult giant pandas. The results showed that the management mode of singleton and parent rearing during cub development and mixed male and female group housing during the stage of subadult learning skills and experience could effectively improve the natural reproduction success rate of captive adult male giant pandas. Using odor stimulation during the mating period could change the courtship behavior of adult giant pandas in captivity, as males, when courting estrous females, behaved in a way that did not lead to successful mating. Applying these results to the breeding management and mating strategies of captive male giant pandas could not only help improve appropriate reproductive behavior and subsequently increase reproductive performance but also may provide more candidates for China's giant panda reintroduction programs.

One strategy to protect endangered species, and improve the quality of habitat to meet the needs of both the wildlife and human communities that rely on large protected areas (such as national park), is by zoning its management for multiple uses. We assessed whether multi-use zoning of the Giant Panda National Park (GPNP) could achieve the goal of protecting the panda population and its habitat, while also promoting community development. We integrate panda presence data, human disturbance distribution, and environmental factors to evaluate panda habitat suitability, the effectiveness of zoning designations, and the impact of human disturbance on panda habitat. Our results show that panda habitat suitability has been partially improved, as certain areas of increased in suitability or stabilized (maintained suitability) across the research region between 2001–2003 and 2011–2013, based on the 3rd and 4th national surveys of the giant panda. Most of the optimum and suitable habitat for panda were located in the core protection area of the GPNP. However, the optimum habitat in the general control area is often located at the junction with the core protection area, indicating a particular need to strengthen management in these areas. Meanwhile, the encounter rates of livestock grazing were highest in optimum habitat and unsuitable habitat. As such, particular attention needs to be paid to the pressures on wildlife caused by human disturbances, such as livestock grazing, in the general control area. Our analyses and these findings have important implications for giant panda conservation and GPNP construction.

To explore the relationship between the development of feeding behaviour and energy intake for captive giant pandas, food intake, feeding rate, and discrimination time were analysed for 26 pandas grouped by sex and age (cub, sub-adult, adult, and elderly). Feeding rates were significantly different between all age groups, except between elderly and adults. In addition, significant differences were found in discrimination time among the female age groups, and all male age groups except between the adults and sub-adults. Among adults in the same age groups, significant differences between the sexes existed in their feeding rate and discrimination time. Differences in discrimination time existed among elderly, adult and sub-adult females. This study of the dynamic characteristics of the feeding behaviour of captive pandas could provide a theoretical basis for feeding recommendations to improve the success of giant panda breeding programmes.

Antioxidant of bamboo leaves (AOB) was certified to be a natural antioxidant by the Chinese Ministry of Health in 2003. However, the effects of AOB on animal reproductive and developmental functions remain unclear. The present study aimed to investigate the effects of different concentrations of AOB on mouse embryonic fibroblast (MEF) cells, and to examine the underlying molecular mechanism through which AOB affects the proliferation and apoptosis of MEFs. MEFs prepared from individual embryos were treated with various dosages of AOB. Cell viability and apoptosis were detected by MTT and flow cytometry assays, respectively. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression. Functional annotation of differentially‑expressed genes was performed according to the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Compared with the control group, ~50% of MEF cells were inhibited following treatment with a 400 µg/ml concentration of AOB. Treatment with 400 µg/ml AOB for 72 h significantly increased the apoptotic rate of MEF cells compared with the control group. Following treatment with AOB, dehydrogenase/reductase 9, phospholipase A2 group IVE and platelet derived growth factor B were downregulated, while 17 other genes were upregulated in MEF cells. Treatment with AOB markedly increased the expression of phosphorylated extracellular signal‑regulated kinase (ERK), β‑catenin, transcription factor SOX‑17, calcium‑binding tyrosine phosphorylation‑regulated protein, and cholesterol side chain cleavage enzyme mitochondrial (P

Targeted therapeutics is used as an alternative treatment of non-small cell lung cancer (NSCLC); however, treatment effect is far from being satisfactory, and therefore identification of new targets is needed. We have previously shown that metuzumab inhibit tumor growth in vivo. The present study was performed to investigate the anti-tumor efficacy of metuzumab combined with gemcitabine and cisplatin (GP), paclitaxel and cisplatin (TP) or navelbine and cisplatin (NP) regimens in multiple NSCLC cell lines. Our results demonstrate that, in comparison to single agent metuzumab or GP treated cells, metuzumab combined with GP display inhibitory effects on tumor growth. Furthermore, we found that metuzumab elevated the sensitivity of cell lines to gemcitabine, which was identified by MTT assay. Flow cytometric analysis showed that metuzumab combined with gemcitabine (GEM) treatment led to an obvious G1 arrest and an elevated apoptosis in A549, NCI-H460 and NCI-H520 cells. Western blot analysis also demonstrated a significantly reduced level of cyclin D1, Bcl-2, and an obviously increase level of Bax and full-length caspase-3 in A549, NCI-H460 and NCI-H520 cells treated with metuzumab/gemcitabine combination in comparison with single agent treated cells. In addition, metuzumab/gemcitabine treated A549, NCI-H460 and NCI-H520 cells also demonstrated a significantly increase in deoxycytidine kinase (dCK) protein level compared with single agent metuzumab or gemcitabine treated cells. Xenograft models also demonstrated that this metuzumab/gemcitabine combination led to upregulation of dCK. Taken together, the mechanisms of metuzumab combined with GP repress tumor growth were that the combined treatment significantly inhibited the tumor cell proliferation, apoptosis and cell cycle in vitro and in vivo and at least partially by induction of dCK expression. Our results suggested that metuzumab could significantly enhance chemosensitivity of human NSCLC cells to gemcitabine. Metuzumab/gemcitabine combination treatment may be a potentially useful therapeutic regimen for NSCLC patients.

Cletus rubidiventris is a crop pest, especially for rice. This study first reported the complete mitochondrial genome of this species. The total length of mitochondrial genome is 15,590 bp and including 13 PCGs, 22 tRNA genes, and 2 rRNA genes, with 31.8% T, 15.8% C, 41.6% A, and 10.8% G. The overall GC content of the genome is 27%. The mitochondrial genome order, nucleotide composition, and codon usage pattern is similar to C. punctiger. The phylogenetic tree shows that C. rubidiventris belong to the Coreidae.